Copathology; Dementia with Lewy bodies; Parkinson disease; Parkinson disease dementia; Tau; α-Synuclein; β-Amyloid; alpha-Synuclein; tau Proteins; Aged; Aged, 80 and over; Alzheimer Disease/genetics; Alzheimer Disease/metabolism; Alzheimer Disease/pathology; Brain/metabolism; Brain/pathology; Female; Humans; Lewy Bodies/genetics; Lewy Bodies/metabolism; Lewy Bodies/pathology; Lewy Body Disease/genetics; Lewy Body Disease/metabolism; Lewy Body Disease/pathology; Male; alpha-Synuclein/genetics; alpha-Synuclein/metabolism; tau Proteins/genetics; tau Proteins/metabolism; A-Synuclein; B-Amyloid; Alzheimer Disease; Brain; Lewy Bodies; Lewy Body Disease; Medicine (all)
Abstract :
[en] Lewy body disorders (LBD) are common neurodegenerative diseases characterized by the presence of aggregated α-synuclein in Lewy bodies and Lewy neurites in the central and peripheral nervous systems. The brains of patients with LBD often display other comorbid pathologies, i.e. insoluble tau, β-amyloid aggregates, TAR DNA-binding protein 43 (TDP-43) deposits, and argyrophilic grain disease (AGD). The incidence and physiological relevance of these concurrent pathological findings remain controversial. We performed a semiquantitative detailed mapping of α-synuclein, tau, β-amyloid (Aβ), TDP-43, and AGD pathologies in 17 areas in 63 LBD cases (44 with Parkinson disease [PD], 28 with dementia, and 19 with dementia with Lewy bodies). APOE and MAPT genetic variants were also investigated. A majority of LBD cases had 2 or 3 concomitant findings, particularly Alzheimer disease-related pathology. Pathological stages of tau, β-amyloid and α-synuclein pathologies were increased in cases with dementia. Aβ score was the best correlate of the time to dementia in PD. In addition, β-amyloid deposition correlated with α-synuclein load in all groups. MAPT H1 haplotype did not influence any assessed pathology in PD. These results highlight the common concurrence of pathologies in patients with LBD that may have an impact on the clinical expression of the diseases.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Colom-Cadena, Martí; Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain ; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain
Grau-Rivera, Oriol; Neurological Tissue Bank, Biobanc Hospital Clínic-IDIBAPS, Barcelona, Spain
Planellas, Lluís; Parkinson's Disease and Movement Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
Cerquera, Catalina; Parkinson's Disease and Movement Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain ; Neurology Unit, Hospital Universitario San Ignacio, School of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia
Morenas, Estrella; Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain ; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain
Helgueta Romero, Sergio ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis
Muñoz, Laia; Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain ; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain
Kulisevsky, Jaime; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain
Marti, Maria Jose; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain ; Parkinson's Disease and Movement Disorders Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain
Tolosa, Eduard; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain ; Neurological Tissue Bank, Biobanc Hospital Clínic-IDIBAPS, Barcelona, Spain
Clarimon, Jordi; Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain ; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain
Lleó, Alberto; Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain ; CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain
Gelpi, Ellen; Neurological Tissue Bank, Biobanc Hospital Clínic-IDIBAPS, Barcelona, Spain
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